# Cytotoxic Agents by the Phosphinoylation and Thiophosphinoylation of 3‑Hydroxy-1,2,3,6-tetrahydrophosphinine 1‑Oxides as β‑Hydroxyphosphonates and -Phosphine Oxides

## TL;DR

Scientists created new cytotoxic compounds by modifying phosphinine oxides, which showed strong effects against cancer cells in lab tests.

## Contribution

The novel contribution is the synthesis and cytotoxic evaluation of phosphinoylated and thiophosphinoylated hydroxy-tetrahydrophosphinine oxides.

## Key findings

- The synthesized compounds significantly reduced cancer cell viability at 100 μM concentration.
- Phosphinoylation and thiophosphinoylation of less hindered isomers was selectively achieved.
- Cytotoxic effects were observed in U266 myeloma and A2058 melanoma cells.

## Abstract

A series of hydroxy-1,2,3,6-tetrahydrophosphinine
oxides were prepared
by the two-step ring enlargement of 1-substituted 3-phospholene 1-oxides
via the corresponding dichlorocarbene adducts. The two diastereomers
of the P-ethoxy-3-phosphabicyclo­[3.1.0]­hexane 3-oxides
could be identified by single crystal X-ray analysis, hence the isomers
could be characterized by NMR methods. Detailed examination of the
crystal structures of the two isomers shows weak O···H
and Cl···H interactions, which are different for the
two isomers, in accord with the different arrangements of the molecules
in the solid state. The less hindered hydroxy-tetrahydrophosphinine
oxide isomers were selectively phosphinoylated and thiophosphinoylated.
The cytotoxic effect of the P-heterocycles synthesized was tested
on U266 myeloma cells and on A2058 melanoma cells. The results are
promising, as the viability of the cells was decreased drastically
at the higher 100 μM concentration, especially in respect of
one hydroxy-tetrahydrophosphinine oxide and the two P-functionalized
derivatives, independently of the substituent’s nature.